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PROBLEM/CONDITION Autism spectrum disorder (ASD). PERIOD COVERED 2018. DESCRIPTION OF SYSTEM The Autism and Developmental Disabilities Monitoring (ADDM) Network conducts active surveillance of ASD. This report focuses on the prevalence and characteristics of ASD among children aged 8 years in 2018 whose parents or guardians lived in 11 ADDM Network sites in the United States (Arizona, Arkansas, California, Georgia, Maryland, Minnesota, Missouri, New Jersey, Tennessee, Utah, and Wisconsin). To ascertain ASD among children aged 8 years, ADDM Network staff review and abstract developmental evaluations and records from community medical and educational service providers. In 2018, children met the case definition if their records documented 1) an ASD diagnostic statement in an evaluation (diagnosis), 2) a special education classification of ASD (eligibility), or 3) an ASD International Classification of Diseases (ICD) code. RESULTS For 2018, across all 11 ADDM sites, ASD prevalence per 1,000 children aged 8 years ranged from 16.5 in Missouri to 38.9 in California. The overall ASD prevalence was 23.0 per 1,000 (one in 44) children aged 8 years, and ASD was 4.2 times as prevalent among boys as among girls. Overall ASD prevalence was similar across racial and ethnic groups, except American Indian/Alaska Native children had higher ASD prevalence than non-Hispanic White (White) children (29.0 versus 21.2 per 1,000 children aged 8 years). At multiple sites, Hispanic children had lower ASD prevalence than White children (Arizona, Arkansas, Georgia, and Utah), and non-Hispanic Black (Black) children (Georgia and Minnesota). The associations between ASD prevalence and neighborhood-level median household income varied by site. Among the 5,058 children who met the ASD case definition, 75.8% had a diagnostic statement of ASD in an evaluation, 18.8% had an ASD special education classification or eligibility and no ASD diagnostic statement, and 5.4% had an ASD ICD code only. ASD prevalence per 1,000 children aged 8 years that was based exclusively on documented ASD diagnostic statements was 17.4 overall (range: 11.2 in Maryland to 29.9 in California). The median age of earliest known ASD diagnosis ranged from 36 months in California to 63 months in Minnesota. Among the 3,007 children with ASD and data on cognitive ability, 35.2% were classified as having an intelligence quotient (IQ) score ≤70. The percentages of children with ASD with IQ scores ≤70 were 49.8%, 33.1%, and 29.7% among Black, Hispanic, and White children, respectively. Overall, children with ASD and IQ scores ≤70 had earlier median ages of ASD diagnosis than children with ASD and IQ scores >70 (44 versus 53 months). INTERPRETATION In 2018, one in 44 children aged 8 years was estimated to have ASD, and prevalence and median age of identification varied widely across sites. Whereas overall ASD prevalence was similar by race and ethnicity, at certain sites Hispanic children were less likely to be identified as having ASD than White or Black children. The higher proportion of Black children compared with White and Hispanic children classified as having intellectual disability was consistent with previous findings. PUBLIC HEALTH ACTION The variability in ASD prevalence and community ASD identification practices among children with different racial, ethnic, and geographical characteristics highlights the importance of research into the causes of that variability and strategies to provide equitable access to developmental evaluations and services. These findings also underscore the need for enhanced infrastructure for diagnostic, treatment, and support services to meet the needs of all children.

En la actualidad la ingesta de nutrientes en la dieta se caracteriza por el contenido de altos niveles de fructosa, un monosacárido encontrado en las frutas y muy usado artificialmente como edulcorante, presente en una amplia variedad de productos procesados, generando, junto a las grasas saturadas, un aumento del contenido calórico de los alimentos. Ese alto contenido calórico en el cual la fructosa aporta de manera considerable, se ha señalado como la causa de trastornos metabólicos. Aunque los azúcares son una fuente de energía inmediata necesaria, su consumo sobrepasa en muchas ocasiones el gasto energético, favoreciendo la síntesis de ácidos grasos, proceso realizado por el hígado; este órgano es un centro de regulación metabólico y a pesar de los mecanismos compensatorios que posee, la ingesta de fructosa en altas cantidades y por periodos prolongados de tiempo puede llevar a desencadenar daño tisular, por lo que es importante dilucidar los mecanismos de daño hepático que se ven reflejados en la pérdida de la funcionalidad. Por lo tanto, el objetivo de esta revisión bibliográfica es documentar la relación del alto consumo de fructosa con el deterioro hepático.

Introduction: Obesity is a public health problem that is associated with cerebrovascular diseases, such as ischemic stroke. The coexistence of obesity with cerebral ischemia has been suggested to be considerably detrimental to the neurological system. Objective: Hence, in this study, we evaluated the long-term effects of a 20% high fructose diet (HFD) and global cerebral ischemia on neurological, cognitive and emotional performance in three-month-old male Wistar rats. Results: Our results demonstrated that fructose intake led to increases in body weight and blood glucose, as well as reduced insulin sensitivity. The co-morbidity of fructose intake and cerebral ischemia resulted to hyperlipidemia, as well as increases in liver and adipocyte damage, which worsened neurological performance and resulted in alterations in learning and emotional skills at two weeks post-ischemia. No significant biochemical changes in autophagy and plasticity markers at the late stage of ischemia were observed. Conclusion: These results suggested that obesity causes a lasting effect on metabolic disorders that can contribute to increased neurological impairment after cerebral ischemia.

Objectives: Cerebral ischemia is caused by a reduction of the blood flow in a specific area in the brain, triggering cellular cascades in the tissue that result in neuronal death. This phenomenon l...

Introducción. La isquemia cerebral es la tercera causa de riesgo de muerte en Colombia y la primera causa de discapacidad física en el mundo. En diversos estudios en los que se silenció la cinasa 5 dependiente de la ciclina (CDK5) se ha demostrado que la reducción de su actividad es beneficiosa frente a la isquemia. Sin embargo, su efecto sobre la neurogénesis después de la isquemia no se ha dilucidado suficientemente.Objetivo. Evaluar el silenciamiento de la CDK5 en la neurogénesis y la gliogénesis después de la isquemia cerebral focal en ratas.Materiales y métodos. Se usaron 40 machos de rata Wistar de ocho semanas de edad. Los grupos de control y los isquémicos sometidos a transducción en la región del hipocampo CA1, se inyectaron intraperitonealmente por estereotaxia con 50 mg/kg de bromodesoxiuridina (BrdU) a partir de las 24 horas y hasta el día 7 después de la isquemia, con un vector viral asociado a adenovirus usando una secuencia no interferente (SCRmiR) y una interferente (CDK5miR). Se evaluó la capacidad neurológica durante los quince días siguientes y se detectó la capacidad de inmunorreacción para la BrdU, la proteína doblecortina (DCX), los núcleos neuronales (NeuN), y la proteína fibrilar acídica de la glía (Glial Fibrillary Acidic Protein, GFAP) a los 15 y 30 días de la isquemia.Resultados. Los animales isquémicos tratados con CDK5miR mejoraron su puntuación neurológica y presentaron un incremento de la BrdU+ a los 15 días de la isquemia, lo cual se correlacionó con una mayor intensidad de la DCX+ y una menor de la GFAP+. No hubo modificación de los NeuN+, pero sí una reducción significativa de la GFAP+ a los 30 días de la isquemia en los animales tratados comparados con los animales isquémicos no tratados.Conclusión. La terapia con CDK5miR generó la recuperación neurológica de ratas isquémicas asociada con la inducción de la neurogénesis y el control de la capacidad de reacción de la proteína GFAP a corto y largo plazo después de la isquemia.

Multiple studies on cerebral ischemia have been performed in animal models to propose different strategies of neuroprotection that mitigate either the early or late consequences of the disease. These therapies have been successful in reducing the volume of infarction, the proinflammatory cascade, and the amount of free radicals, as well as reversing markers of neurodegeneration, among other events. However, when those strategies are translated to clinical studies, their effectiveness is not reproduced. This review will focus on highlighting some of the main limitations of the animal models of stroke that lead to unsuccessful translational therapies and the common risk factors in humans that should be carefully considered in the experimental design of future studies to generate a more realistic spatiotemporal physiopathology and improve therapeutic efficacy in cerebral ischemia.

Sporadic Alzheimer's disease (SAD) is the most common form of dementia, and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most frequent hereditary ischemic small vessel disease of the brain. Relevant biomarkers or specific metabolic signatures could provide powerful tools to manage these diseases. Therefore, the main goal of this study was to compare the postmortem frontal cortex gray matter, white matter and cerebrospinal fluid (CSF) between a cognitively healthy group and CADASIL and SAD groups. We evaluated 352 individual lipids, belonging to 13 lipid classes/subclasses, using mass spectrometry, and the lipid profiles were subjected to multivariate analysis to discriminate between the dementia groups (CADASIL and SAD) and healthy controls. The main lipid molecular species showing greater discrimination by partial least squares-discriminant analysis (PLS-DA) and a higher significance multivariate correlation (sMC) index were as follows: phosphatidylserine (PS) PS(44:7) and lysophosphatidylethanolamine (LPE) LPE(18:2) in gray matter (GM); phosphatidylethanolamine (PE) PE(32:2) and phosphatidylcholine PC PC(44:6) in white matter (WM), and ether PE (ePE) ePE(38:2) and ether PC (ePC) ePC(34:3) in CSF. Common phospholipid molecular species were obtained in both dementias, such as PS(44:7) and lyso PC (LPC) LPC(22:5) in GM, PE(32:2) in WM and phosphatidic acid (PA) PA(38:5) and PC(42:7) in CFS. Our exploratory study suggests that phospholipids (PLs) involved in neurotransmission alteration, connectivity impairment and inflammation response in GM, WM and CSF are a transversal phenomenon affecting dementias such as CADASIL and SAD independent of the etiopathogenesis, thus providing a possible common prodromal phospholipidic biomarker of dementia.

Objective: To evaluate the role of regulatory T cells (Tregs) at late stages of stroke. Methods: Anti-CD25 antibody (or PBS as a control) was injected to reduce the pool of Tregs in Wistar rats; then, ischemia was induced transiently by middle cerebral artery occlusion during 60 min and reperfusion was allowed for 7 d. Then, Treg frequency was analyzed in peripheral blood, spleen and lymph nodes. Neurological score (0-6) and infarct volume were also determined. Results: Nine days after injection, the CD4+ CD25+ T cells were reduced by 70.4%, 44.8% and 57.9% in peripheral blood, spleen and lymph nodes, respectively compared to PBS-treated rats. In contrast, the reduction of CD4+ FOXP3+ T cells was lower in the same compartments (38.6%, 12.5%, and 29.5%, respectively). The strongest reduction of CD25+ CD4+ T cells was observed in those FOXP3-negative cells in blood, spleen and lymph nodes (77.8%, 52.8%, and 60.7%, respectively), most likely corresponding to activated T cells. Anti-CD25-treated transient middle cerebral artery occlusion rats had a lower neurological deficit and did not develop tissue damage compared with PBS-treated animals. Conclusions: These findings suggest that treatment with anti-CD25 in our model preferentially reduce the T cell population with an activated phenotype, rather than the Treg population, leading to neuroprotection by suppressing the pathogenic response of effector T cells. COL0070457 COL0012444 COL0010744 COL0008639

Cerebrovascular accident (CVA) is the second leading cause of death in the world and the first cause of disability in adults, being a 34% of affected people younger than 65 years old. Which is an important consequence by sedentary lifestyle and a high intake of fats and sugars. One of the major shortcomings of current therapeutical approach is the lack of comorbidity studies, intervention time (less than 4.5 h) and the short time of protection or follow-up study, which unprotect for long-term sequelae in the patients. Gene therapy has been shown to be a very useful tool for the treatment of neurodegenerative diseases; specifically in cerebral ischemia there are few experimental studies, which are mentioned in this chapter. The most of them have a pretreatment approach, which does not facilitate the clinical translation, therefore, a major challenge of gene therapy is that it to be implemented as post-injury therapy, which is supported by our results using shRNAmiR carried out in adeno associated viral vector, preventing and reversing neurodegeneration, neurovascular unit uncoupling and cognitive impairment, which could be relevant in the field of translational medicine.

Statins are potent cholesterol biosynthesis inhibitors that exert protective effects in humans and in experimental models of stroke. The mechanisms involved in these protective actions are not completely understood. This study evaluates whether atorvastatin (ATV) treatment affects the GluN1 and GluN2B subunits of the N-methyl-D-aspartic acid receptor in the somatosensory cerebral cortex at short and long periods following ischemia. Sham and ischemic male Wistar rats received 10 mg/kg of ATV or placebo by gavage every 24 hr for 3 consecutive days. The first dose was administered 6 hr after ischemia–reperfusion or the sham operation. ATV treatment resulted in faster recovery of neurological scores than placebo, prevented the appearance of pyknotic neurons, and restored microtubule-associated protein 2 and neuronal nuclei staining to control values in the somatosensory cerebral cortex and the hippocampus at 72 hr and 15 days postischemia. Furthermore, ATV prevented spatial learning and memory deficits caused by cerebral ischemia. Cerebral ischemia reduced the number of GluN1/PSD-95 and GluN2B/PSD-95 colocalization clusters in cortical pyramidal neurons and reduced the levels of brain-derived neurotrophic factor (BDNF) in the cerebral cortex. These effects of the ischemic insult were prevented by ATV, which also induced GluN2B/PSD-95 colocalization in neuronal processes and an association of GluN2B with TrkB. The GluN2B pharmacological inhibitor ifenprodil prevented the increase in BDNF levels and the motor and cognitive function recovery caused by ATV in ischemic rats. These findings indicate that GluN2B is involved in the neuroprotective mechanism elicited by ATV to promote motor and cognitive recovery after focal cerebral ischemia. © 2014 Wiley Periodicals, Inc.

Regulatory T cells (Tregs) inhibit the activation of the immune response which could down-regulate the systemic and focal activation observed during ischemic stroke. In fact, in animal models, Tregs infiltrate the infarcted brain and reduce the pro-inflammatory cytokine production and infarct volume, mainly in late stages of ischemia. Recently, an expansion and greater suppressive capacity of circulating Tregs after treatment with statins was observed, in addition to their cardio- and neuroprotective actions demonstrated previously. Thus, to determine whether Treg modulation mediated by statins can also be beneficial during stroke, cerebral ischemia was artificially induced in Wistar rats by transient middle cerebral artery occlusion (tMCAO) during 60 minutes with subsequent reperfusion for 7 days. Six hours after surgery, some animals were treated with atorvastatin (ATV, 10 mg/kg) or carboxymethylcellulose as vehicle at the same concentration every other day during 7 days. Some animals were sham operated as control group of surgery. Interestingly, ATV treatment prevented the development of infarct volume, reduced the neurological deficits, and the circulating and cervical lymph node CD25+FoxP3+ Treg population. Moreover, there was a reduction of glial cell activation, which correlated with decreased circulating Tregs. Remarkably, treatment with ATV induced an increase in the frequency of CD4+CD25+ T cells, in particular of those expressing CTLA-4, in brain samples. Together, these results suggest that ATV can modulate Tregs in peripheral tissue and favor their accumulation in the brain, where they can exert neuroprotective actions maybe by the reduction of glial cell activation.

During the estrous cycle, a remodeling of synapses on somas and dendritic spines occurs in the rat hypothalamic arcuate nucleus. The synaptic remodeling is known to be induced by estradiol, but the molecular mechanisms involved still have not been fully clarified β-Catenin is known to regulate synaptic plasticity, so we have assessed possible modifications of β-catenin in the rat mediobasal hypothalamus during the estrous cycle. Our findings indicate that β-catenin expression is increased during proestrus and estrus in comparison with diestrus day. This increase was accompanied by an enhanced phosphorylation of Akt in Ser473 and of glycogen synthase kinase-3β (GSK3β) in Ser9. Also, the association of β-catenin with the synaptic protein PSD95 was increased during these same stages of the estrous cycle, whereas the levels of synapsin I were significantly decreased in proestrus. These findings suggest that Akt/GSK3β/β-catenin signaling is involved in the synaptic modifications that occur in the basal hypothalamus during the estrous cycle. © 2012 Wiley Periodicals, Inc.

Stroke is the second most common cause of death in people over 45 years of age in Colombia and is the leading cause of permanent disability worldwide. Cerebral ischemia is a stroke characterized by decreased blood flow due to the occlusion of one or more cerebral arteries, which can cause memory problems and hemiplegia or paralysis, among other impairments. The literature contains hundreds of therapies (invasive and noninvasive) that exhibit a neuroprotective effect when evaluated in animal models. However, in clinical trials, most of these drugs do not reproduce the previously demonstrated neuroprotective property, and some even have adverse effects that had not previously been detected in animal experimentation. Statins are drugs that inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol synthesis. Several studies have shown that statin therapy in an animal model of focal cerebral ischemia reduces infarct volume, as well as markers of neurodegeneration, activates neuronal survival pathways, and improves performance on learning and memory tests. Given the implied therapeutic benefit and the limited understanding of the mechanism of action of statins in brain repair, it is necessary to address the biochemical and tissue effects of these drugs on synaptic proteins, such as NMDA receptors, synaptic adhesion proteins, and cytoskeletal proteins; these proteins are highly relevant therapeutic targets, which, in addition to giving a structural account of synaptic connectivity and function, are also indicators of cellular communication and the integrity of the blood–brain barrier, which are widely affected in the long term post-cerebral infarct but, interestingly, are protected by statins when administered during the acute phase.

Las enfermedades cerebrovasculares se han convertido en un problema de salud mundial debido a su alta tasa de mortalidad y discapacidad. En Colombia constituyen la tercera causa de riesgo de muerte y en el mundo son la primera causa de discapacidad física y mental. Se han evaluado muchas estrategias terapéuticas en modelos experimentales y en ensayos clínicos sin buenos resultados. Algunas de las falencias de los estudios sobre tales estrategias terapéuticas son el reducido tiempo de intervención (menos de cuatro horas y media), así como el poco tiempo de protección y la falta de seguimiento de la terapia, lo cual genera secuelas a largo plazo en los pacientes. La terapia génica ha demostrado ser una herramienta de gran utilidad para el tratamiento de las enfermedades neurodegenerativas; sin embargo, en el caso específico de la isquemia cerebral hay pocos estudios experimentales. En nuestras investigaciones hemos constatado el potencial de la terapia génica basada en el ARN de interferencia para prevenir y revertir la neurodegeneración y el deterioro cognitivo después de un infarto cerebral, aunque todavía deben sortearse algunas dificultades terapéuticas inherentes al sistema nervioso cerebral, así como concertar los intereses de los diversos sectores involucrados: el Gobierno, las empresas y el sector científico y académico, con el fin de incentivar la inversión y facilitar la aplicación en otras partes del país de las terapias promisorias propuestas en nuestra región para disminuir las secuelas de enfermedades crónicas no transmisibles, entre ellas la incapacidad física y mental después de un infarto cerebral. Cerebrovascular disease has become a worldwide health problem due to its high mortality and disability rate. It is the third leading cause of death risk in our country and the first cause of physical and mental disability in the world. Many therapeutic strategies have been evaluated both in experimental models and in clinical trials without success. One of the major shortcomings of these therapeutic studies is the limitation in the intervention time (less than four and a half hours) and the short time of protection or follow-up of the therapy, which generates long-term sequelae in the patients. Gene therapy has been shown to be a very useful tool for the treatment of neurodegenerative diseases; however, experimental studies are few, specifically in cerebral ischemia. Our research has demonstrated the potential benefit of RNA interference based gene therapy to prevent and reverse neurodegenerative effects and cognitive impairment following a stroke. However, therapeutic difficulties inherent to the cerebral nervous system should be overcome, and the interests of government, business and scientific and academic sectors should be coordinated to procure investment and to facilitate the translation of promising therapies proposed from our region aimed at reducing the sequelae of chronic non-communicable diseases, including physical and mental disability after a stroke.

International audience; Rho-kinase (ROCK) is a downstream effector of RhoA, which has been associated with growth cone collapse and retraction in neurons. ROCK inhibition has been shown to protect against ischemic damage, thereby improving short-term collateral flow, inhibiting platelet aggregation, leukocyte adhesion, and preventing neuronal death. However, little is known about the long-term effects of ROCK inhibition on behavior and neuroprotection. The consequence of ROCK inhibition on ischemic rats' learning and spatial memory after 30 days of intracerebroventricular treatment was evaluated. It was found that Y27632 (ROCK inhibitor) reduced neurodegenerative markers, such as Fluoro-Jade, PHF (paired helicoidal filaments) immunoreactivity, and p25 protein levels, in the hippocampus of ischemic animals and improved learning and spatial memory tasks. However, Y27632 alone impaired sham animals' long-term memory. These findings demonstrated the beneficial impact of ROCK inhibition on tauopathy and altered p25 protein levels following global cerebral ischemia.